Obesity, the most prevalent, fatal, chronic disease of the 21st Century, is increasing at a rate seen before only with infectious diseases. Morbid obesity, the most severe form, afflicts 23 million Americans. These individuals are not only limited by their bulk but are sharply compromised by life-endangering co-morbidities. Surgery has proven to be an effective therapy. The Greenville gastric bypass operation (GGB), developed at this institution, produces not only durable weight loss greater than 100 Ibs but also induces full remission of type 2 diabetes in 83 percent of patients, control of hypertension in over half, as well as full reversal of such co-morbidities as asthma, Pickwickian syndrome, stress incontinence, and pseudotumor cerebri. The reproducible reversal of type 2 diabetes in GGB patients is a provocative finding and requires further basic research. However, the GGB, like other bariatric procedures, is associated with serious long-term nutritional deficiencies and, in vulnerable individuals, emotional disorders. Generally, there is no consensus about which of the seven common bariatric procedures should be used. There is also considerable variation in surgical outcomes across the US for the same operation due to a lack of standardization of the surgical care. Thus, bariatric surgery is ripe for a collaborative approach to answering both clinical and basic research issues. Our current center efforts include three major areas: 1. Fostering collaboration within the bariatric surgical community to promote clinical, behavioral, and basic research in morbid obesity and its co-morbidities; 2. Clinical studies of the efficacy, efficiency, and safety of two types of gastric bypass operations with an emphasis on differences in outcomes between African-American and Caucasian women. 3. Basic science studies of insulin action and sensitivity in human subjects prior to and after bariatric surgery. In addition, this application includes three proposals for inter-institutional projects: 1. Comparison of the most commonly performed bariatric operations; 2. the mechanism for increased insulin sensitivity after gastric bypass surgery; and 3. the ethics of the informed consent in bariatric surgery. Because East Carolina University has a productive tradition of interdisciplinary clinical, basic science, and behavioral research in morbid obesity as well as a record of national leadership, we submit this application to become one of the Bariatric Surgery Clinical Centers of the NIDDK.